The goal of this project is to identify new anthelmintics and/or nematicides, referred to generically as anti-nematode drugs, which have novel modes of action. The approach is comprised of four steps: 1) Identify a compound which is active on the model nematode Caenorhabditis elegans (at this step potency of the compound is unimportant). 2) Establish that the compound's mode of action is novel using a unique technology, called NemaScreen, which involves analyzing the efficacy of the compound on each member of a library of drug-resistant mutants of C. elegans. Novel compound are defied as those which are effective on all of the mutants in the library. 3) Isolate new mutants which are resistant to the novel compound. 4) Establish ligand binding assays for the new target and for homologous targets in mammals. The new mutants provide a site-specific screen for new compounds which act on the same target., The ligand binding assays facilitate structure activity studies designed to identify compounds which are nematode specific. The approach is designed to be carried out in collaboration with major pharmaceutical and/or agricultural chemical companies.